In Vivo Interaction of Cis‐platinum and Fosfomycin on Squamous Cell Carcinoma

AbstractObjectives/Hypothesis Cis‐platinum is the most frequently used chemotherapeutic agent for the treatment of head and neck squamous cell carcinoma (SCCA). Ototoxicity and nephrotoxicity continue to be the primary dose‐limiting toxicities encountered. Fosfomycin, a broad‐spectrum antibiotic, has been previously shown to be both otoprotective and nephroprotective against cis‐platinum toxicity. Previous in vitro work demonstrated that fosfomycin does not inhibit the tumoricidal actions of cis‐platinum. This study tests whether fosfomycin inhibits cis‐platinum in vivo.Methods An SCCA cell line was grown in vivo in four groups of nude mice, which then received no treatment, standard‐dose cis‐platinum, high‐dose cis‐platinum, or high‐dose cis‐platinum with fosfomycin.Results Fosfomycin did not inhibit the tumoricidal activity of cis‐platinum. Mice treated with fosfomycin also had longer survival, which is probably due to lessening of immediate cis‐platinum systemic toxicity.Conclusion This study shows that fosfomycin in combination with cis‐platinum may be useful in treating advanced, and possibly relatively chemoresistant, SCCA of the head and neck.